The long range objectives of the proposed studies are to evaluate the metabolic alterations in the mother which may lead to abnormal outcome and place the infant at risk for morbidity, death and brain damage. Although the effects of maternal diabetes and intrauterine growth retardation upon the newborn have been known for sometime, only recently have the methods for safely quantifying these changes in the mother and the infant been developed. The final goal of these studies is to be able to intervene in the presence of aberrations in metabolism and successfully treat the fetus. It is hypothesized that provisions of a normal intrauterine environment will prevent abnormalities of development which commence during the fetal period. Specifically the primary objectives are to: (a) document the adaptive metabolic changes which occur during normal pregnancy not only to understand the normal state, but also to define pathways for intervention; (b) document the alterations in maternal metabolism in the diabetic pregnancy and correlate these changes with alterations in the neonatal metabolism; (c) document the alterations in maternal metabolism when fetal growth retardation is identified; and (d) as fetal growth retardation is the result of decreased delivery of substrates, these studies propose to examine maternal responses to nutrient deprivation in animal studies. In the proposed studies, the relationships between three major metabolic fuels, glucose, fat and amino acids will be examined by quantifying the turnover rates of principal substrates by using safe non-radioactive stable isotopic tracers and gas chromatography-mass spectrometry. The total energy consumption and the types of fuels consumed will be quantified by indirect respiratory calorimetry. In response to maternal diabetes and aberrant fetoplacental metabolism in the IUGR, the relationship between substrate supply and hormonal regulation is altered and thus one may expect abnormalities in the regulation of substrate turnover during fasting. The long range objective of these studies is to measure these anticipated abnormalities, to examine the optimal methods for their regulation antenatally, and to evaluate the efficacy of such interventions.